Carbonic anhydrase inhibitors are used in the treatment of ocular hypertension (cause of the onset of glaucoma). European patent EP 296 879 B1 describes that, among other compounds, 4-(N-alkylamino)-5,6-dihydro-4H-thieno-[2,3-b]-thiopyran-2-sulfonamide-7,7-dioxides of general formula (VII)
wherein R1 is an alkyl and R2 is a hydrogen atom or an alkyl, have carbonic anhydrase inhibitory activity when topically administered.
Among such compounds, the compound (4S,6S)-4-(N-ethylamino)-5,6-dihydro-6-methyl-4H-thieno-[2,3-b]-thiopyran-2-sulfonamide-7,7-dioxide, also known as dorzolamide, of formula:
stands out.
Patent documents and applications EP 296 879 B1, U.S. Pat. No. 5,157,129, EP 617 037 and WO 02/20529 describe several synthetic routes for obtaining dorzolamide and analogues.
Documents U.S. Pat. No. 5,157,129 and WO 02/20529 describe enantioselective routes in which the sulfonamide group in position 2 is introduced in the final steps of the synthesis without affecting the stereochemistry of the intermediates. One of the key intermediates in both cases is the compounds with an amino group in position 4, of formula (II):

and its diastereoisomers.
To obtain it, U.S. Pat. No. 5,157,129 starts from a hydroxyl group in position 4, which is subjected to a tosylation reaction and subsequent nucleophilic substitution with an alkylamine:

However, the introduction of the tosyl group is hindered due to the lack of reactivity of the hydroxyl group. Furthermore, once the compound is tosylated, as this is in a benzyl position, it is unstable and therefore susceptible to producing lateral reactions, such as the elimination, substitution with a chlorine group in the reaction conditions (if tosyl chloride is used) and if a compound is involved which has a sulfone group in position 6, even the substitution thereof with an oxygen for the sulfonyl group can occur.
There are few methods for converting a benzyl alcohol into the corresponding alkylamine in a completely diastereoselective manner. For example, U.S. Pat. No. 5,391,772 describes the introduction of an azide group on similar structures, also starting from a hydroxyl group in position 4, by means of the use of a phosphoryl azide group which results in inverting the configuration. In this case, however, prior synthesis of the phosphoryl azide is required, and the use of azides entails a certain hazard at the industrial level due to their toxicity and because they are potentially explosive.
Therefore, according to the state of the art, obtaining the alkylamines of formula (II) has several drawbacks because it involves at least 3-4 synthesis steps, some of which are hazardous. All this may further affect the diastereoselectivity in the subsequent amination, as well as the occurrence of byproducts.